Enhancement of Noradrenergic Phenotype Expression in Transgenic Mice Overexpressing V-1, A Cytoplasmic Ankyrin Repeat Protein

Catecholaminergic cells exhibit three types of transmitter phenotypes: dopaminergic, noradrenergic and adrenergic. The catecholaminergic phenotypes are thought to be determined by a phenotype-specific coordinate regulation of gene expression of the four catecholamine synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). However, molecular mechanisms that control the coordinate transcriptional regulation of these genes remain to be fully elucidated, although the second messenger systems and transcription factors involved in catecholaminergic cell-specific gene expression for catecholamine synthesizing enzymes have been so far identified and extensively investigated (Zetterstrom et al., 1997; Morin et al., 1997; Lo et al., 1999). Recently, an ankyrin repeat protein designated V-1 has been suggested to act as a possible coordinate regulator for the expression of genes encoding catecholamine synthesizing enzymes, since it has been demonstrated that stable overexpression of V-1 protein in the catecholaminergic cell line, PC12D cell, augments the expression of transcripts encoding TH, AADC and DBH, and as a resuit, catecholamine production is upregulated (Yamakuni et al., 1998). V-1 is a 12 kDa protein containing 2.5 copies of the ankyrin repeat, which has been originally isolated as a developmentally regulated protein from murine cerebellum (Taoka et al., 1992).